Hell Lena, Däullary Thomas, Burghart Vanessa, Mauracher Lisa-Marie, Grilz Ella, Moser Bernhard, Kramer Gero, Schmid Johannes A, Ay Cihan, Pabinger Ingrid, Thaler Johannes
Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria.
Center for Physiology and Pharmacology, Institute of Physiology, Medical University of Vienna, 1090 Vienna, Austria.
Cancers (Basel). 2021 Mar 24;13(7):1487. doi: 10.3390/cancers13071487.
Patients with advanced prostate cancer may develop fulminant disseminated intravascular coagulation (DIC). Circulating extracellular vesicles (EVs)-exposing tissue factor (TF), the initiator of the coagulation cascade, may play an important role. We included 7 prostate cancer patients with DIC, 10 age- and stage-matched cancer controls without DIC, and 10 age-matched healthy male individuals. EV-TF activity was highly elevated in prostate cancer patients with DIC (11.40 pg/mL; range: 4.34-27.06) compared with prostate cancer patients without DIC (0.09 pg/mL; range: 0.00-0.30, = 0.001) and healthy controls (0.18 pg/mL; range: 0.09-0.54; = 0.001). Only EVs from patients with DIC reduced fibrin clot formation time of pooled plasma in a TF-dependent manner. Next, we performed in vitro co-culture experiments including EVs derived from a prostate cancer cell line with high (DU145) and low (LNCaP) TF expression, peripheral blood mononuclear cells (PBMCs), and platelets. Co-incubation of DU145 EVs with PBMCs and platelets significantly increased EV-TF activity in conditioned medium and induced TF activity on monocytes. No such effects were seen in co-culture experiments with LNCaP EVs. In conclusion, the findings indicate that elevated EV-TF activity plays a role in the development of prostate-cancer-related DIC and may result from interactions between tumor-derived EVs, monocytes, and platelets.
晚期前列腺癌患者可能会发生暴发性弥散性血管内凝血（DIC）。循环中暴露组织因子（TF）的细胞外囊泡（EVs）作为凝血级联反应的启动因子，可能起着重要作用。我们纳入了7例患有DIC的前列腺癌患者、10例年龄和分期匹配但无DIC的癌症对照者以及10例年龄匹配的健康男性个体。与无DIC的前列腺癌患者（0.09 pg/mL；范围：0.00 - 0.30，P = 0.001）和健康对照者（0.18 pg/mL；范围：0.09 - 0.54；P = 0.001）相比，患有DIC的前列腺癌患者的EV - TF活性显著升高（11.40 pg/mL；范围：4.34 - 27.06）。只有来自DIC患者的EVs以TF依赖的方式缩短了混合血浆的纤维蛋白凝块形成时间。接下来，我们进行了体外共培养实验，包括来自高TF表达（DU145）和低TF表达（LNCaP）的前列腺癌细胞系的EVs、外周血单核细胞（PBMCs）和血小板。DU145 EVs与PBMCs和血小板共同孵育显著增加了条件培养基中的EV - TF活性，并诱导了单核细胞上的TF活性。在与LNCaP EVs的共培养实验中未观察到此类效应。总之，研究结果表明，升高的EV - TF活性在前列腺癌相关DIC的发生中起作用，可能源于肿瘤来源的EVs、单核细胞和血小板之间的相互作用。
